tbuckley/cabot-search huggingface dataset:
NADOM trial: Neoadjuvant/adjuvant trial of darovasertib in ocular melanoma (OM).
Authors: Roderick O'day, Max Conway, Li-Anne Lim, John McKenzie, Victoria Atkinson, William Glasson, Lindsay McGrath, Svetlana Cherepanoff, Elin Gray, Matthew A. Maurer, Michael O'Quigley, Mark J. Shackleton, Anthony M. Joshua
Journal: Journal of Clinical Oncology (2023)

TPS9612 Background: Darovasertib (Daro) is a novel inhibitor of PKC, that has pre-clinical activity in GNAQ/GNA11 tumours including ocular melanoma. A recently completed clinical trial of Daro monotherapy in metastatic OM with a response rate of 11%, and DCR of 78% with only mild manageable toxicity, suggesting utility in localized disease and in the adjuvant setting. Methods: NADOM is an investigator-initiated window-of-opportunity phase 2 clinical trial open in 3 centers across Australia. Eligible patients include patients planned for enucleation, ECOG 0-1 with adequate organ function. The primary objective is the feasibility and safety of neoadjuvant Daro in a pilot cohort of 12 patients. Secondary objectives include the effect of Daro on circulating biomarkers (including CTCs and ctDNA), imaging assessments (MRI, FDG-PET and ocular ultrasound), pharmacokinetic and pharmacodynamic correlates and radiographic PFS in the adjuvant setting. Treatment comprises a neo-adjuvant period of treatment of up to 6 months at ophthalmologist discretion with Daro (300mg bid) before definitive management. Patients who demonstrated radiological, biomarker or clinical response are then offered an adjuvant period of treatment for up to 6 months following integrated consensus at multi-disciplinary ocular oncology meetings. DSMB meetings are scheduled to ensure clinical and peri-operative safety regularly. Enrolment commenced in November 2022 and accrual is ongoing in the 6 month neo-adjuvant cohort. Results: To date, an initial safety cohort of 1 month of neo-adjuvant treatment has been cleared following DSMB review. Conclusions: Recruitment is ongoing and expected to complete in late 2023. Clinical trial information: NCT05187884 .
Dissecting small cell lung cancer subtypes with cell-free DNA fragmentomes.
Authors: Lorenzo Rinaldi, Zachary L. Skidmore, Bahar Alipanahi, Garrett Graham, Bryan Chesnick, Nobuyuki Takahashi, Rajesh Kumar, Shubhank Goyal, Melissa Lauren Abel, Justin Malin, Parth Anil Desai, Nicholas C. Dracopoli, Victor E. Velculescu, Anish Thomas, Alessandro Leal
Journal: Journal of Clinical Oncology (2023)

8592 Background: Although small cell lung cancer (SCLC) is managed as a single cancer type, new evidence supports that subtypes (high vs low neuroendocrine) of SCLC acquire diverse transcriptional and epigenetic states. Furthermore, distinct SCLC subtypes acquire unique therapeutic vulnerabilities, such as the low-neuroendocrine highly inflamed SCLC subtype that has been linked to immunotherapy sensitivity. We have previously shown that DELFI (DNA evaluation of fragments for early interception) can be used to non-invasively distinguish SCLC from non-small cell lung cancer (NSCLC). Here, we report a preliminary analysis of using the DELFI approach for distinguishing among SCLC subtypes. Methods: Circulating cell-free DNA (cfDNA) was isolated from plasma samples of patients diagnosed with relapsed SCLC and treated with durvalumab plus olaparib in a phase II trial (NCT02484404). Over 200 cfDNA libraries were prepared for whole genome sequencing in batches with internal controls. To infer tumor gene expression profiles in cfDNA, we investigated genome-wide signals of tissue-specific transcription factors differentially regulated in SCLC, and applied a novel DELFI-based approach to inform SCLC molecular subtypes. Clinical information, patient-matched tissue transcriptome (RNA-seq), and chromatin accessibility data (ATAC-seq) were examined in orthogonal analyses. Results: The DELFI classifier detected SCLC cases (N = 47) with a median DELFI score of 1.0 (95% CI 0.99-1), significantly higher than previously reported scores for other lung cancer subtypes. Comparison of DELFI fragmentome signals to publicly available tumor transcriptomes shows subtype-level concordance ( r = 0.78, p &lt; 0.001, Pearson), particularly in pre-treatment SCLC cases separating high- vs low- neuroendocrine subtypes. High-neuroendocrine SCLCs exhibited a decrease in aggregate cfDNA fragment coverage at ASCL1 transcription factor binding sites relative to low-neuroendocrine SCLCs (r = 0.90, p &lt; 0.001, Pearson). Additionally, low-neuroendocrine SCLCs revealed a significant decrease in aggregate cfDNA fragment coverage at genomic binding sites regulated by hematopoietic transcription factors, reflecting the inflamed phenotype of this SCLC subtype. Integration of these approaches provided a cfDNA fragmentation-based machine learning model that distinguished SCLC subtypes with high performance. Conclusions: Genome-wide cfDNA fragmentome analyses can differentiate high- and low-neuroendocrine SCLC subtypes. Given the challenges for performing SCLC biopsies in a clinical setting, we believe this approach could be a viable method of subtyping SCLC in a non-invasive manner.
Talk, test, and take one click to curb prostate cancer mortality.
Authors: Sandhya Cautha, Shekhar Bhatta, Asona Lui, Valentina Moirangthem, Thanh-Ha T. Luong, David Ferris, Kevin R. Jain
Journal: Journal of Clinical Oncology (2023)

6541 Background: Prostate cancer remains the most commonly diagnosed cancer and the second leading cause of cancer-related death in men in the United States. BronxCare Health System (BCHS) serves the Bronx neighborhoods of Morris Heights, Fordham South, and Mount Hope, notable for the highest prostate cancer incidence rate in New York City as per the American Cancer Society Cancer Action Network report 2019, highlighting the need for prostate cancer screening among the patient population we serve. An anonymous voluntary paper survey was performed in 2019 at BCHS to determine primary care physician understanding and implementation of current PSA testing guidelines. The study showed that primary care providers at BCHS approach PSA testing in a wide variety of ways and screen a wide age range of patients suggesting a need for intervention. An electronic medical record (EMR) decision support tool activated during primary care visits for men aged 55-69 years was implemented beginning January 1, 2021 which facilitates the provider and patient engagement in a shared decision-making discussion. This a follow-up study to determine the effect of this EMR application on PSA order rates and prostate cancer diagnosis rates at BCHS. Methods: The total number of patients who had PSA and lipid panel (LP) screening were extracted from the EMR of BCHS for potentially eligible men (aged 55-69) seen during primary care visits during the years 2016-2022. LP is done annually as a part of routine screening for adults aged 55-69 and is taken as an equivalent of primary care visits. PSA screening rates were compared to LP screening rates to control for unforeseen variables. Similarly, the number of newly-diagnosed prostate cancers among the same population of men was extracted for the years 2016-2021. Data for 2022 is still not available. 2016-2020 are pre-EMR and 2021 and 2022 are post-EMR flag years. The pre and post-EMR flag PSA and prostate cancer diagnosis numbers were compared by calculating Z scores and p-values. Results: The year-wise PSA, LP, and newly-diagnosed prostate cancers (PC) are tabulated below. The proportion of men who had PSA testing among all men aged 55-69 who had LP testing in each pre-EMR flag year was compared to each post-EMR flag year. A significant increase (p &lt; 0.00001) was noted in the proportion of men who had PSA screening after implementation of the EMR application. Similarly, the proportion of men with newly-diagnosed prostate cancer among all men aged 55-69 who had PSA screening significantly increased after EMR application (p &lt; 0.00001). Conclusions: A decision support tool embedded in the EMR has been an effective approach in increasing prostate cancer screening rates and may help curb prostate cancer mortality in our patient population as early detection in right men at the right age has the potential to reduce prostate cancer mortality. [Table: see text]
High-confidence AI-based biomarker profiling for H&amp;E slides to optimize pathology workflow in lung cancer.
Authors: Efrat Ofek, Razan Haj, Yossef Molchanov, Rinat Yacobi, Chen Mayer, Tilda Barliya, Inbal Gazy, Addie Dvir, Ido Hayun, Jonathan Zalach, Nurit Paz Yaacov, Nir Peled, Jair Bar, Iris Barshack
Journal: Journal of Clinical Oncology (2023)

e21207 Background: In recent years AI methodologies have been increasingly adopted in the oncology space as part of the clinical decision process. Our previous research has shown accurate detection of actionable biomarkers based on AI algorithms applied to Hematoxylin &amp; Eosin (H&amp;E) scanned slides. While investigating a wide actionable biomarker panel, this profiling process can also flag patients with no actionable biomarkers. In Non-Small Cell Lung Cancer (NSCLC), EGFR, ALK, and ROS1 are the most commonly tested actionable alterations and the primary exclusion criteria for immunotherapy. Here we present a novel AI-based solution that can accurately and almost instantaneously detects patients without the main actionable biomarkers from the H&amp;E image alone, thus helping prioritize the pathology lab workflow and navigate patients to a faster and more optimal diagnosis route. Methods: A retrospective cohort of 435 NSCLC patients was collected from the Sheba Medical Center pathology department. All cases (from primary and metastatic sites) with documented results for EGFR mutations, ALK, and ROS1-fusions were included. Molecular profiling was based on Oncomine Comprehensive, Dx target, or Solid tumor DNA assays, with 4 cases also supported by the Idylla EGFR mutation test. Deidentified digital whole slide images (WSIs) were run using Imagene’s AI classifier and compared to the officially reported results. The classifier was generated using self-supervised algorithm, combined with multiple instance learning algorithms applied using untagged and tagged FFPE H&amp;E scan (40x or 20x magnification) from Imagene’s internal database (including TCGA research network slides). A categorical prediction (positive/negative) inferred on the validation set by the combined AI classifier model. Results: The combined AI model for detecting EGFR, ALK and ROS1 actionable alteration resulted in 127 patients (29.4% of the cohort) reported with no EGFR actionable mutation, ALK, or ROS1 fusions. Only two patients (1.57% of the negatively detected patients) were found to be false negative ( EGFR: p.G719D and p.L858R), demonstrating 98.43% accuracy. Conclusions: Image-based molecular detection can serve as an accurate and fast detection method to be used in the clinical setting for monitoring and prioritizing current pathology workflow. Specifically, it can detect a major fraction of the non-targetable patients and optimize their diagnostic flow.
Efficacy of nivolumab and relatlimab-rmbw in patients with advanced melanoma who were previously treated with PD-1 inhibitor: Real world experience.
Authors: Sekwon Jang, Chelsea Stahl, Jafar Al-Mondhiry, Suraj S Venna
Journal: Journal of Clinical Oncology (2023)

e21533 Background: Nivolumab and relatlimab-rmbw (R/N) combination demonstrated superior efficacy to nivolumab alone in patients with previously untreated metastatic or unresectable melanoma. Sparse data exists on the efficacy of this combination in patients with melanoma that relapsed after,or was resistant to treatment with PD-1 inhibitors. Methods: We conducted a retrospective study of patients with unresectable or metastatic melanoma whose disease recurred or progressed on/after prior PD-1 inhibitor who received R/N at Inova Schar Cancer Institute. Efficacy endpoint was objective response using modified RECIST1.1. Unconfirmed complete response (CR) or partial response (PR) were included in objective response rate (ORR). Patients whose Positron Emission Tomography (PET) scan showing complete metabolic resolution of metastatic sites were also considered CR. Patients who had rapid clinical progression and didn’t have repeat radiologic studies were considered to have progressive disease (PD). Patients who underwent radiation to target lesions were considered non-evaluable (NE). Results: From Sep 2021 through Dec 2022, a total of 32 patients (19 male) received R/N including 8 unresectable stage III melanomas and 24 stage IV melanomas (M1a: 4, M1b: 4, Mc1: 5, M1d: 10). Median age was 67 (39-88), and 12 (38%) had BRAF mutation. Median number of prior therapies was 2 (range: 1-7) including anti-CTLA4 antibody in 22 and BRAF/MEK inhibitor in 8. Nine patients (28%) had ≥ 3 prior therapies. Among 30 patients evaluable for response, ORR was 33% (4 CR, 6 PR). Three had stable disease (SD), and 16 had PD including 2 with rapid clinical progression. Response by subgroup is included in table. Conclusions: R/N shows clinically meaningful antitumor activity in patients who received prior PD-1 inhibitor in real world setting. Additional clinical data of R/N in PD-1 inhibitor relapsed or refractory patients are needed to validate the results of this single-center study. [Table: see text]
Income level as a prognostic factor in non-dedifferentiated liposarcoma.
Authors: Christopher Reese Bine, Marco Braaten, Eric Nielsen, Alec Czaplicki, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2023)

e23558 Background: Liposarcoma is the most common soft tissue sarcoma and primarily arises in subcutaneous fat of the lower extremities. Previous research has shown socioeconomic factors (eg. Income, insurance status, facility type) to be strongly associated with patterns of care as well as overall survival in bone and soft tissue sarcoma patients. Using the NCDB, this study analyzed the association between income and survival in patients with non-dedifferentiated liposarcoma. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with Liposarcoma from 2004 to 2019 using the histology codes 8850, 8851, 8852, 8853, 8855, and 8857 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 27 and statistical significance was set at α = 0.05. Results: Of 4631 patients included in the sample, 1508 (32.5%) were from the highest income ( &gt; $46,000) bracket. High-income patients experienced longer mean overall survival (149 months) compared to middle (136.5 months) and low (130 months) income patients (p &lt; 0.001). After controlling for age, tumor size, stage, and surgery of primary site, low-income patients experienced higher hazard ratios relative to the middle- and high-income groups (HR1.56; p &lt; 0.001). On presentation, higher income patients had less co-morbidities, and tumors which were less aggressive (grade) and advanced (NCDB stage &amp; metastasis) (p &lt; 0.001). Furthermore, they were more likely to undergo surgery (90.3%) and had the shortest interval between diagnosis and definitive surgical procedure (p &lt; 0.001). No differences were seen in surgical margins, palliative care, tumor size, or radiation dose. Conclusions: This study found that high-income patients with non-dedifferentiated liposarcoma experience improved overall survival and expedited surgery compared to middle- and low-income groups. Further research could elucidate the true cause of this disparity.
Do external factors such as weather affect patient reported outcomes of patients with malignant diseases?
Authors: Hanna Salm, Martin Eichler, Jeanette Bahr, Dimosthenis Andreou, Daniel Pink
Journal: Journal of Clinical Oncology (2023)

e18715 Background: The QLQ-C30 is one of the most widely used patient-reported outcome (PRO) instrument to assess health-related quality of life in cancer patients developed by the European Organization for Research and Treatment of Cancer (EORTC). Even if only little scientific evidence is published on this topic, patients often report that their emotional and physical state varies depending on climatic conditions. To enhance the understanding of quality of life in cancer patients, this study analyzed whether external factors like weather data and season can influence PRO measures and cancer patients’ well-being. Methods: Over a period of 12 months data was obtained from inpatient and outpatient cancer patients in two German cancer centers using the QLQ-C30. Items were assigned to five functional scales, three symptom scales, a global health status/QoL scale, and a number of single items assessing symptoms commonly reported by cancer patients.Patients were approached by their medical oncologist or nursing staff to complete the questionnaire anonymously once or multiple times. QoL data were linked to weather factors including temperature, hours of sunshine and season. Results: We received a total of n = 5040 responses (54 % male). Regarding global health status/QoL, the best result was recorded at 25 - 30 degrees, and the lowest value was measured at 5 - 10 degrees (mean 61.3 vs. 52.6, p &lt; 0.001). Insomnia was most pronounced at &lt; = 0 degrees and least present at 25 – 30 degrees (mean 39.3 vs. 29.5, p &lt; 0.001). Overall, best scores were obtained at 25 – 30 degrees, whereas quality of life and symptom burden were worst at 5 – 10 degrees. Global health/QoL was highest at 8 hours of sunshine and lowest at 0 hours of sunshine (mean 56.9 vs. 50.9, p .003). Global health/QoL was lower in winter months than in summer (mean 53.8 vs. 57.4, p &lt; 0.001) presenting highest scores in June and July. Conclusions: The findings of our study indicate that quality of life in cancer patients as well as PROs can be influenced systematically by external factors like season or weather conditions. This could possibly also be of importance when interpreting the results of studies that use standardized instruments to assess health-related quality of life in cancer patients -e.g., if the questionnaires were only answered in certain month (summer/winter) or under external conditions that were not evenly distributed.
Understanding the information needs of lymphoma and CLL patients: A comparison of Asia-Pacific and Europe.
Authors: Cherie D. Bates, Amanda Watson, Lorna Warwick
Journal: Journal of Clinical Oncology (2023)

e18884 Background: Effective communication between healthcare providers and patients has improved patient outcomes and satisfaction. This study aims to evaluate the impact of healthcare provider-patient communication on patient satisfaction and outcomes in patients diagnosed with lymphoma and chronic lymphocytic leukaemia (CLL). The study utilises data from the Lymphoma Coalition (LC) 2020 Global Patient Survey (GPS) to compare the information experiences of patients in the Asia-Pacific (APAC) and European regions diagnosed with lymphoma and CLL. Methods: We analysed a subset of patients from APAC region (n = 3021) and the European region (n = 4343) and examined the demographic characteristics of both groups. Statistical analyses, including chi-square tests and logistic regression, were performed using IBM SPSS v27 software to assess patients' information experiences. Results: The findings of this study reveal that patients in APAC experienced a lower likelihood of receiving sufficient information at the time of diagnosis and expressed challenges in comprehending treatment options and managing treatment-related side effects. Notably, compared to patients in Europe, patients in APAC reported a greater need for information related to self-care (42% vs 14%) and treatment options (68% vs 50%). Conclusions: This study highlights APAC patients with lymphoma &amp; CLL require more information, reflective of their health literacy levels, from their healthcare professionals. It is recommended that healthcare providers provide tailored information to improve patient outcomes and satisfaction. [Table: see text]
Clinical outcomes and national information of patients with multiple myeloma (MM) covered under the largest national health insurance in a low-middle-income country.
Authors: Milton Alberto Lombana Quinonez, Jorge Enrique Sabogal, Guido Gonzalez, Ana Milena Torres
Journal: Journal of Clinical Oncology (2023)

e18561 Background: In Colombia, national health insurance is private in all the country, with coverage greater than 95% of population. However, there is few health outcomes published in specific neoplastic diseases. We analyze relevant clinical outcomes and the information known by the largest health insurer Nueva EPS (NEPS) in a major region of Colombia, in patients with MM, which could allow decision-making in public health. Methods: Pts treated under the Valle del Cauca regional NEPS insurance with a diagnosis of MM between 1996 and 2018 and who received care at comprehensive cancer centers, were retrospectively identified. We collect relevant variables from the institutional electronic medical records and the information available from the insurer. Our primary objective was to determine the overall survival (OS) in general and specific populations and what was the important clinical information that could be extracted directly by the insurer to analyze and support decisions. We performed Kaplan Meier, and cox regression analysis with relevant variables. Results: 233 pts treated in 3 comprehensive cancer care centers in the city of Cali were included. Median overall survival was 68 months, with 25% alive at 15 years. Age &gt; 75 years [HR 2.4, 95%CI 1.5-4, P = 0.0001], ISS category [HR 1.7, 95%CI 1.0-2.9, P = 0.003], and chronic kidney disease [HR 3.6, 95%CI 1.9- 6.7, P = 0.0004] were associated with a higher risk of death. Receiving an autologous transplant [HR 0.2, 95% CI 0.1-0.6, P = 0.0006] and the use of proteasome inhibitors and or immunomodulators were associated with better survival (OS 54 vs 15 months, p = 0.05). This contrasts with the scarce data available at the insurer, with information about heavy chain involved in only 63% of pts, light chain 44%, Durie-Salmon stage 54%, ISS stage 31%, FISH studies in 16%, type of 1st line of treatment in 65%, objective response 26% and overall survival in 72%. Conclusions: The survival of patients with MM treated under the largest health insurer in Colombia was good and similar to international series in highly experienced centers, however the relevant clinical information known by the insurer was poor. This supports the need to develop and have a single national electronic medical record that allows a better access to health data for decision-making in public health.